Predicting response: noradrenaline reuptake inhibition

For the past decade, the role of noradrenaline in depression has been somewhat neglected in favour of serotonin. This is largely because of the advent of the selective serotonin reuptake inhibitors, which have facilitated clinical and experimental observation of the roles of serotonin. Until now, no such tools have been available to study the noradrenergic system. However, the recent development of reboxetine, the first selective noradrenaline reuptake inhibitor, has allowed clinical investigation of the role of the noradrenergic system in different aspects of depressive disorders. In clinical trials, the use of reboxetine has shown that selective noradrenaline reuptake inhibition is an effective approach to alleviating depression. It is more effective than placebo and at least as effective as desipramine, imipramine and fluoxetine in the short term. In addition, its efficacy is maintained in patients with severe depression and in those receiving long-term maintenance treatment. Reboxetine is very well tolerated, as predicted from its pharmacological profile, having fewer anticholinergic side-effects than imipramine or desipramine. Compared with fluoxetine, patients treated with reboxetine experienced less nausea and sexual dysfunction, adverse events that are common among those taking selective serotonin reuptake inhibitors. Adverse events predicted by the neuroanatomy of the noradrenergic system, such as tremor and cardiovascular effects, occurred less frequently than expected. Clinical experience with reboxetine challenges our current knowledge of the role of noradrenaline in depression and questions existing evidence based on studies with noradrenergic tricyclic antidepressants. Selective noradrenaline reuptake inhibition, as exemplified by reboxetine, therefore offers a significant improvement in antidepressant pharmacotherapy, and an opportunity to increase our understanding of the role of noradrenaline in depression.